When this project originated, its purpose was to determine the precise factors regulating phagocyte migration to sites of infection and inflammation, focusing on the initial interaction of the cell with extracellular signaling molecules known as chemoattractants. Examples of phagocyte chemoattractants include bacterially-derived N-formyl peptides, the complement-derived peptide C5a, and a large class of structurally related peptides known as chemokines. More recently, this project has expanded to include lymphocyte chemoattractant receptors. Moreover, we have discovered that various microbial pathogens, including HIV, exploit chemoattractant receptors as part of their life cycle. Thus, our specific objectives have also expanded to include the following: (i) to determine the structure of distinct chemoattractant receptors; (ii) to determine the chemical mechanism of activation and regulation of chemoattractant receptors; (iii) to delineate the signal transduction pathways activated by chemoattractants; (iv) to determine the general and specialized biological roles of each chemoattractant receptor; and (v) to delineate the biological role and the mechanism of action of chemoattractant receptors in microbial pathogenesis.